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Overview

Uniprot IDP49917
Protein NameDNA ligase 4
Gene NameLIG4
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
636 KAAPKMKKVIGIIEH

Function

DNA ligase involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination (PubMed:12517771, PubMed:17290226, PubMed:23523427, PubMed:29980672, PubMed:33586762, PubMed:8798671, PubMed:9242410, PubMed:9809069). Catalyzes the NHEJ ligation step of the broken DNA during DSB repair by resealing the DNA breaks after the gap filling is completed (PubMed:12517771, PubMed:17290226, PubMed:9242410, PubMed:9809069). Joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction (PubMed:12517771, PubMed:17290226, PubMed:9242410, PubMed:9809069). LIG4 is mechanistically flexible: it can ligate nicks as well as compatible DNA overhangs alone, while in the presence of XRCC4, it can ligate ends with 2-nucleotides (nt) microhomology and 1-nt gaps (PubMed:17290226). Forms a subcomplex with XRCC4; the LIG4-XRCC4 subcomplex is responsible for the NHEJ ligation step and XRCC4 enhances the joining activity of LIG4 (PubMed:9242410, PubMed:9809069). Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends (PubMed:10854421). LIG4 regulates nuclear localization of XRCC4 (PubMed:24984242)

Protein Sequence

10 MAASQTSQTV 20 ASHVPFADLC 30 STLERIQKSK 40 GRAEKIRHFR 50 EFLDSWRKFH 60 DALHKNHKDV 70 TDSFYPAMRL 80 ILPQLERERM 90 AYGIKETMLA 100 KLYIELLNLP 110 RDGKDALKLL 120 NYRTPTGTHG 130 DAGDFAMIAY 140 FVLKPRCLQK 150 GSLTIQQVND 160 LLDSIASNNS 170 AKRKDLIKKS 180 LLQLITQSSA 190 LEQKWLIRMI 200 IKDLKLGVSQ 210 QTIFSVFHND 220 AAELHNVTTD 230 LEKVCRQLHD 240 PSVGLSDISI 250 TLFSAFKPML 260 AAIADIEHIE 270 KDMKHQSFYI 280 ETKLDGERMQ 290 MHKDGDVYKY 300 FSRNGYNYTD 310 QFGASPTEGS 320 LTPFIHNAFK 330 ADIQICILDG 340 EMMAYNPNTQ 350 TFMQKGTKFD 360 IKRMVEDSDL 370 QTCYCVFDVL 380 MVNNKKLGHE 390 TLRKRYEILS 400 SIFTPIPGRI 410 EIVQKTQAHT 420 KNEVIDALNE 430 AIDKREEGIM 440 VKQPLSIYKP 450 DKRGEGWLKI 460 KPEYVSGLMD 470 ELDILIVGGY 480 WGKGSRGGMM 490 SHFLCAVAEK 500 PPPGEKPSVF 510 HTLSRVGSGC 520 TMKELYDLGL 530 KLAKYWKPFH 540 RKAPPSSILC 550 GTEKPEVYIE 560 PCNSVIVQIK 570 AAEIVPSDMY 580 KTGCTLRFPR 590 IEKIRDDKEW 600 HECMTLDDLE 610 QLRGKASGKL 620 ASKHLYIGGD 630 DEPQEKKRKA 640 APKMKKVIGI 650 IEHLKAPNLT 660 NVNKISNIFE 670 DVEFCVMSGT 680 DSQPKPDLEN 690 RIAEFGGYIV 700 QNPGPDTYCV 710 IAGSENIRVK 720 NIILSNKHDV 730 VKPAWLLECF 740 KTKSFVPWQP 750 RFMIHMCPST 760 KEHFAREYDC 770 YGDSYFIDTD 780 LNQLKEVFSG 790 IKNSNEQTPE 800 EMASLIADLE 810 YRYSWDCSPL 820 SMFRRHTVYL 830 DSYAVINDLS 840 TKNEGTRLAI 850 KALELRFHGA 860 KVVSCLAEGV 870 SHVIIGEDHS 880 RVADFKAFRR 890 TFKRKFKILK 900 ESWVTDSIDK 910 CELQEENQYL I

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000781 chromosome, telomeric region
Cellular Component GO:0000793 condensed chromosome
Cellular Component GO:0032807 DNA ligase IV complex
Cellular Component GO:0005958 DNA-dependent protein kinase-DNA ligase 4 complex
Cellular Component GO:0070419 nonhomologous end joining complex
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0003910 DNA ligase (ATP) activity
Molecular Function GO:0003909 DNA ligase activity
Molecular Function GO:0016874 ligase activity
Molecular Function GO:0000287 magnesium ion binding
Biological Process GO:0006284 base-excision repair
Biological Process GO:0051301 cell division
Biological Process GO:0008283 cell population proliferation
Biological Process GO:0071479 cellular response to ionizing radiation
Biological Process GO:0007417 central nervous system development
Biological Process GO:0051276 chromosome organization
Biological Process GO:0071897 DNA biosynthetic process
Biological Process GO:0006302 double-strand break repair
Biological Process GO:0097680 double-strand break repair via classical nonhomologous end joining
Biological Process GO:0006303 double-strand break repair via nonhomologous end joining
Biological Process GO:0075713 establishment of integrated proviral latency
Biological Process GO:0033152 immunoglobulin V(D)J recombination
Biological Process GO:0001701 in utero embryonic development
Biological Process GO:0045190 isotype switching
Biological Process GO:0043524 negative regulation of neuron apoptotic process
Biological Process GO:0051402 neuron apoptotic process
Biological Process GO:0006297 nucleotide-excision repair, DNA gap filling
Biological Process GO:2001252 positive regulation of chromosome organization
Biological Process GO:0048146 positive regulation of fibroblast proliferation
Biological Process GO:0050769 positive regulation of neurogenesis
Biological Process GO:0002328 pro-B cell differentiation
Biological Process GO:0010332 response to gamma radiation
Biological Process GO:0010165 response to X-ray
Biological Process GO:0000012 single strand break repair
Biological Process GO:0035019 somatic stem cell population maintenance
Biological Process GO:0033077 T cell differentiation in thymus
Biological Process GO:0033153 T cell receptor V(D)J recombination
Biological Process GO:0033151 V(D)J recombination

Reference

[1] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.